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Abstract Background Conflicting findings regarding the impact of High protein intake during the early phase in critically ill patients have been reported. Therefore, we aimed to assess the influence of higher early protein intake on the prognosis of critically ill patients. Methods This randomized controlled trial involved 173 critically ill patients who stayed in the Intensive Care Unit/Emergency ICU (ICU/EICU) for at least 7 days. The Low group (n = 87) and High group (n = 86) received protein supplementation of 0.8 g/kg.d and 1.5 g/kg.d, respectively, within 1–3 days of enteral nutrition (EN) initiation, with both groups transitioning to 1.5 g/kg.d on the 4th day. The serum prealbumin (PA), blood urea nitrogen/creatinine, and rectus femoris muscle thickness and cross-sectional area of all patients was measured on the 1th, 3rd, 5th, 7th day, and the day of ICU/EICU discharge. Results Patients in both Low and High groups showed no significant differences in age, APACHE II scores, or other demographic and baseline characteristics. There were also no significant differences in the primary outcome (28-day mortality rate) and secondary outcomes (incidence rate of refeeding syndrome and EN tolerance score) between the two groups. However, the Low group exhibited a significantly higher 28-day mortality rate (HR = 2.462, 95% CI: 1.021–5.936, P = 0.045) compared to High group, as determined by Cox proportional hazards models incorporating the time factor. The High group exhibited significantly shorter durations of mechanical ventilation and ICU stay compared to the Low group. Serum PA levels were higher, and rectus femoris muscle atrophy rates were lower in the High group. Furthermore, for septic patients, high protein intake significantly reduced the 28-day mortality rate despite a small sample size (n = 34). Conclusions Our study indicates that increasing early protein intake to 1.5 g/kg.d may be safe and help improve the nutritional status and prognosis of critically ill patients. Trial registration This study was registered with the Chinese Clinical Trial Registry (ChiCTR2000039997, https://www.chictr.org.cn/ ).

Abstract Cation exchanger (CAX) genes play an important role in plant growth/development and response to biotic and abiotic stresses. Here, we tried to obtain important information on the functionalities and phenotypic effects of CAX gene family by systematic analyses of their expression patterns, genetic diversity (gene CDS haplotypes, structural variations, gene presence/absence variations) in 3010 rice genomes and nine parents of 496 Huanghuazhan introgression lines, the frequency shifts of the predominant gcHaps at these loci to artificial selection during modern breeding, and their association with tolerances to several abiotic stresses. Significant amounts of variation also exist in the cis-regulatory elements (CREs) of the OsCAX gene promoters in 50 high-quality rice genomes. The functional differentiation of OsCAX gene family were reflected primarily by their tissue and development specific expression patterns and in varied responses to different treatments, by unique sets of CREs in their promoters and their associations with specific agronomic traits/abiotic stress tolerances. Our results indicated that OsCAX1a and OsCAX2 as general signal transporters were in many processes of rice growth/development and responses to diverse environments, but they might be of less value in rice improvement. OsCAX1b, OsCAX1c, OsCAX3 and OsCAX4 was expected to be of potential value in rice improvement because of their associations with specific traits, responsiveness to specific abiotic stresses or phytohormones, and relatively high gcHap and CRE diversity. Our strategy was demonstrated to be highly efficient to obtain important genetic information on genes/alleles of specific gene family and can be used to systematically characterize the other rice gene families.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2, SARS2) is responsible for the COVID-19 pandemic and infections that continue to affect the lives of millions of people worldwide, especially those who are older and/or immunocompromised. The SARS2 main protease enzyme, Mpro (also called 3C-like protease, 3CLpro), is a bona fide drug target as evidenced by potent inhibition with nirmatrelvir and ensitrelvir, the active components of the drugs Paxlovid and Xocova, respectively. However, the existence of nirmatrelvir and ensitrelvir-resistant isolates underscores the need to develop next-generation drugs with different resistance profiles and/or distinct mechanisms of action. Here, we report the results of a high-throughput screen of 649,568 compounds using a cellular gain-of-signal assay. In this assay, Mpro inhibits expression of a luciferase reporter, and 8,777 small molecules were considered hits by causing a gain in luciferase activity 3x SD above the sample field activity (6.8% gain-of-signal relative to 100 µM GC376). Single concentration and dose-response gain-of-signal experiments confirmed 3,522/8,762 compounds as candidate inhibitors. In parallel, all initial high-throughput screening hits were tested in a peptide cleavage assay with purified Mpro and only 39/8,762 showed inhibition. Importantly, 19/39 compounds (49%) re-tested positive in both SARS2 assays, including two previously reported Mpro inhibitors, demonstrating the efficacy of the overall screening strategy. This approach led to the rediscovery of known Mpro inhibitors such as calpain inhibitor II, as well as to the discovery of novel compounds that provide chemical information for future drug development efforts.

Atherosclerosis is a chronic inflammatory disease characterized by innate and adaptive immune responses, which seriously threatens human life and health. It is a primary cause of coronary heart disease, myocardial infarction, and peripheral vascular disease. Research has demonstrated that immune cells are fundamental to the development of atherosclerosis and chronic inflammation. Therefore, it is anticipated that immunotherapy targeting immune cells will be a novel technique in the management of atherosclerosis. This article reviews the growth of research on the regulatory role of immune cells in atherosclerosis and targeted therapy approaches. The purpose is to offer new therapeutic approaches for the control and treatment of cardiovascular illnesses caused by atherosclerosis.

Abstract Background High‐frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS. Objective The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high‐frequency rTMS) and explore the optimal high‐frequency rTMS on an animal PD model. Methods Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid‐induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored. Results We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain‐derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT‐2) and the suppression of TNF‐α and IL‐1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest. Conclusions Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.

High content Styrene-butadiene-styrene (SBS) modified asphalt binder is commonly used for permeable pavements attribute to reasonable adhesion ability, deformation resistance and toughness. However, due to the large difference in molecular weight between styrene-butadiene-styrene block copolymer and asphalt, the compatibility between SBS and asphalt has always been a key issue restricting its development. To improve the compatibility of high content SBS modified asphalt, the preparation process of high content SBS modified asphalt (shear time, temperature, rate, modifier content) was investigated by orthogonal experimental design method. The effects of modifiers (polyphosphoric acid, montmorillonite, and sulfur) on the physical properties and compatibility of high content SBS modified asphalt were investigated by physical property tests, storage stability tests and dynamic shear rheology tests. The results shows that all three additives have improved the storage stability of high content SBS-modified asphalt, among which, nano montmorillonite has the best comprehensive improvement effect. In addition, the preparation process of high content SBS modified asphalt will also affect its physical properties and compatibility. When the content of MMT and SBS is 2% and 8% respectively, the shear temperature is 170 °C, the shear rate is 4000 rpm, and the shear time is 150 min, the high and low temperature performance of high content SBS modified asphalt is good and the compatibility is the best.

The drilling of printed circuit board (PCB) using micro-drills is an important processing method in modern industry. A protective film with good lubricating and anti-wear properties is generally applied to improve the processing problems of micro-drills during operation. In this study, the effects of C2H2 flow rate on the microstructure, mechanical, and tribological properties of a-C:H films deposited by plasma enhanced chemical vapor deposition (PECVD) technique were investigated. The results showed that when the C2H2 flow rate was low, varying the flow rate had little effect on the microstructure of the prepared a-C:H films. However, when the C2H2 flow rate was greater than 210 sccm, the increase in flow rate caused large particles of carbon clusters to aggregate on the surface of a-C:H films, which resulting in an increase Ra value. Not only did it reduce the adhesion between the film and the substrate, but it also deteriorated the mechanical and tribological properties of the a-C:H film produced. In addition, a-C:H films were also deposited on the micro-drill, and were used for drilling tests on the PCBs to evaluate its servce capability. The optimal parameters of a-C:H film deposited on the micro-drill surface were obtained by observing the morphology of the micro-drill surface after drilling and the hole accuracy statistics. The results showed that a-C:H film deposited on the surface of the micro-drill showed the best machining performance when the C2H2 flow rate was 180 sccm. The surface wear of micro-drill was minimal, the entanglement of tangled chips was minimal. The value of the process capability index (CPK) after 500, 1000, and 2000 drilling of PCB boards was 5.95, 4.33, and 3.15 respectively, which showed the highest drilling accuracy. This is mainly attributed to the better overall properties of the a-C:H films prepared at C2H2 flow rate of 180 sccm, such as lower surface roughness, lowest residual stress, higher hardness, better adhesion, and lower friction coefficient.

Abstract Adipose tissue macrophages can promote beige adipose thermogenesis by altering local sympathetic activity. Here, we perform sympathectomy in mice and further eradicate subcutaneous adipose macrophages and discover that these macrophages have a direct beige-promoting function that is independent of sympathetic system. We further identify adipocyte Ets1 as a vital mediator in this process. The anti-inflammatory M2 macrophages suppress Ets1 expression in adipocytes, transcriptionally activate mitochondrial biogenesis, as well as suppress mitochondrial clearance, thereby increasing the mitochondrial numbers and promoting the beiging process. Male adipocyte Ets1 knock-in mice are completely cold intolerant, whereas male mice lacking Ets1 in adipocytes show enhanced energy expenditure and are resistant to metabolic disorders caused by high-fat-diet. Our findings elucidate a direct communication between M2 macrophages and adipocytes, and uncover a function for Ets1 in responding to macrophages and negatively governing mitochondrial content and beige adipocyte formation.

PurposeTo investigate the therapeutic efficiency of a novel drink termed “Ferment” in cases of ulcerative colitis (UC) and its influence on the gut microbiota.MethodIn this study, we developed a complex of mixed fruit juice and lactic acid bacteria referred to as Ferment. Ferment was fed to mice for 35 days, before inducing UC with Dextran Sulfate Sodium Salt. We subsequently investigated the gut microbiome composition using 16S rRNA sequencing.ResultAfter Ferment treatment, mouse body weight increased, and animals displayed less diarrhea, reduced frequency of bloody stools, and reduced inflammation in the colon. Beneficial bacteria belonging to Ileibacterium, Akkermansia, and Prevotellacea were enriched in the gut after Ferment treatment, while detrimental organisms including Erysipelatoclostridium, Dubosiella, and Alistipes were reduced.ConclusionThese data place Ferment as a promising dietary candidate for enhancing immunity and protecting against UC.

Methane (CH4) is a greenhouse gas as well as being flammable and explosive. In this manuscript, quartz-enhanced photoacoustic spectroscopy (QEPAS) and heterodyne QEPAS (H-QEPAS) exploring a self-designed quartz tuning fork (QTF) with resonance frequency (f0) of ∼8.7 kHz was utilized to achieve sensitive CH4 detection. Compared with the standard commercial 32.768 kHz QTF, this self-designed QTF with a low f0 and large prong gap has the merits of long energy accumulation time and low optical noise. The strongest line located at 6057.08 cm−1 in the 2v3 overtone band of CH4 was chosen as the target absorption line. A diode laser with a high output power of > 30 mW was utilized as the excitation source. Acoustic micro-resonators (AmRs) were added to the sensor architecture to amplify the intensity of acoustic waves. Compared to the bare QTF, after the addition of AmRs, a signal enhancement of 149-fold and 165-fold were obtained for QEPAS and H-QEPAS systems, respectively. The corresponding minimum detection limits (MDLs) were 711 ppb and 1.06 ppm for QEPAS and H-QEPAS sensors. Furthermore, based on Allan variance analysis the MDLs can be improved to 19 ppb and 27 ppb correspondingly. Compared to the QEPAS sensor, the H-QEPAS sensor shows significantly shorter measurement timeframes, allowing for measuring the gas concentration quickly while simultaneously obtaining f0 of QTF.

Abstract Background Dysfunctional attitudes, which are characterized by distorted self-cognitions, were considered to be linked to personality traits. It was found that certain personality traits may predict dysfunctional attitudes in patients with major depressive disorder (MDD). Nonetheless, the relationship between personality traits and dysfunctional attitudes remains under-researched. Aims The aim of this study is to examine the relationship between specific domains of Sixteen Personality Factor (16PF) and dysfunctional attitudes in Chinese participants with or without MDD. In addition, the present study explores the associations between 16PF and eight subtypes of dysfunctional attitudes, based on the proposed eight-factor structure of the Chinese version of the Dysfunctional Attitude Scale-Form A (C-DAS-A). Methods One hundred and sixty-eight participants with MDD and 130 healthy participants were included in the study (Trial Registration Number: ChiCTR1800014591). Personality was assessed using the 16PF Questionnaire. Dysfunctional attitudes were measured through the C-DAS-A. Results The 16PF dimensions associated with dysfunctional attitudes and the eight subtypes were mainly concentrated in the four anxiety facets including factors C, L, O, and Q4, in both MDD and HC groups. There were significant differences in the 16 PF dimensions that would explain dysfunctional attitudes between the two groups, which were as follows: factors C, G, and O in the MDD group, and factors L and Q4 in the HC group. Conclusions Personality traits, especially the anxiety-related personality traits, were distinctly associated with the development of dysfunctional attitudes in people with or without MDD.

Abstract Background Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. Aims In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. Methods SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. Results In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. Conclusions In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.

Base editors of the Cas9 system have been widely used for precise nucleotide substitution in crops. In this study, Cas12a was applied to construct plant cytosine base editors (CBEs). The main elements of Cas12a-CBEs were engineered and their efficiency was evaluated in stably transformed rice cells. An optimized ttCas12a-hyA3Bctd editor, consisting of a LbCas12a variant carrying catalytic inactive D832A and temperature-tolerance D156R double mutations, a truncated human APOBEC3B deaminase, a human RAD51 single-stranded DNA-binding domain, and double copies of UGI, outperformed other Cas12a-CBEs in base editing efficiency. In T0 transgenic rice plants, ttCas12a-hyA3Bctd edited an average of 42.01% and a maximum of 68.75% of lines at six genomic targets. A-to-G conversions were generated in rice by an adenine base editor with a similar architecture to the optimized CBE. Our results provide preliminary evidence for the feasibility of robust and efficient plant Cas12a base editing systems, which could be useful for precise crop breeding.

BackgroundInflammatory bowel disease (IBD) greatly affects human quality of life. Mannose has been reported to be used to treat IBD, but the mechanism is currently unknown.MethodsC57/BL mice were used as research subjects, and the mouse acute colitis model was induced using dextran sulfate sodium salt (DSS). After oral administration of mannose, the body weights and disease activity index (DAI) scores of the mice were observed. The colon lengths, histopathological sections, fecal content microbial sequencing, colon epithelial inflammatory genes, and tight junction protein Occludin-1 expression levels were measured. We further used the feces of mice that had been orally administered mannose to perform fecal bacterial transplantation on the mice with DSS-induced colitis and detected the colitis-related indicators.ResultsOral administration of mannose increased body weights and colon lengths and reduced DAI scores in mice with DSS-induced colitis. In addition, it reduced the expression of colon inflammatory genes and the levels of serum inflammatory factors (TNF-α, IL-6, and IL-1β), further enhancing the expression level of the colonic Occludin-1 protein and alleviating the toxic response of DSS to the intestinal epithelium of the mice. In addition, gut microbial sequencing revealed that mannose increased the abundance and diversity of intestinal flora. Additionally, after using the feces of the mannose-treated mice to perform fecal bacterial transplantation on the mice with DSS-induced colitis, they showed the same phenotype as the mannose-treated mice, and both of them alleviated the intestinal toxic reaction induced by the DSS. It also reduced the expression of intestinal inflammatory genes (TNF-α, IL-6, and IL-1β) and enhanced the expression level of the colonic Occludin-1 protein.ConclusionMannose can treat DSS-induced colitis in mice, possibly by regulating intestinal microorganisms to enhance the intestinal immune barrier function and reduce the intestinal inflammatory response.

Abstract INTRODUCTION We assessed whether midlife sensory and motor functions added to prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS) improve risk predictions of 10‐year changes in biomarkers of neurodegeneration and Alzheimer's disease. METHODS Longitudinal data of N = 1529 (mean age 49years) Beaver Dam Offspring Study participants from baseline, 5‐year, and 10‐year follow‐up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function measures improves CAIDE or FRS risk predictions of 10‐year incidence of biomarker positivity of serum‐based neurofilament light chain (NfL) and amyloid beta (Aβ)42/Aβ40 using logistic regression. RESULTS Adding sensory and motor measures to CAIDE‐only and FRS‐only models significantly improved NfL and Aβ42/Aβ40 positivity predictions in adults above the age of 55. DISCUSSION Including midlife sensory and motor function improved long‐term biomarker positivity predictions. Non‐invasive sensory and motor assessments could contribute to cost‐effective screening tools that identify individuals at risk for neurodegeneration early to target interventions and preventions. Highlights Sensory and motor measures improve risk prediction models of neurodegenerative biomarkers Sensory and motor measures improve risk prediction models of AD biomarkers Prediction improvements were strongest in late midlife (adults >55 years of age) Sensory and motor assessments may help identify high‐risk individuals early

Abstract INTRODUCTION We aimed to assess whether midlife sensory and motor functions improve risk prediction of 10‐year cognitive decline and impairment when added to risk prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS). METHODS Longitudinal data of N = 1529 (mean age 49 years; 54% women) Beaver Dam Offspring Study (BOSS) participants from baseline, 5 and 10‐year follow‐up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk predictions of 10‐year cognitive decline or cognitive impairment incidence using logistic regressions. RESULTS Adding sensory and motor measures to CAIDE‐only and FRS‐only models significantly improved areas under the curve for cognitive decline and impairment models. DISCUSSION Including midlife sensory and motor function improved risk predictions of long‐term cognitive decline and impairment in middle‐aged to older adults. Sensory and motor assessments could contribute to cost‐effective and non‐invasive screening tools that identify high‐risk individuals earlier to target intervention and prevention strategies. Highlights Sensory and motor measures improve risk prediction models of cognitive decline. Sensory and motor measures improve risk prediction models of cognitive impairment. Prediction improvements were strongest in midlife (adults

Abstract Panax ginseng products can be adulterated with materials from other Panax species. The purpose of this study is to provide a rapid P. ginseng authentication method for simultaneous identification of P. ginseng and detection of adulteration in ginseng products at different processing stages. First, a tetra-primer ARMS–PCR assay was designed based on a single-nucleotide polymorphism (SNP) within the trnL-trnF region and was tested at 28 PCR cycles with DNA extracted from Botanical Reference Materials (BRMs). Next, 5′ end random nucleotide and 3′ terminus phosphorothioates linkage modifications were incorporated into the inner primers to improve sensitivity and specificity at 40 PCR cycles. Finally, the modified assay was validated using characterized market ginseng materials and the detection limit was determined. The modified tetra-primer ARMS–PCR assay can achieve the desired sensitivity and specificity using one set of reaction conditions in ginseng materials at different stages. In validation, it was able to correctly identify target species P. ginseng and differentiate it from closely related species. This study suggests that the modified tetra-primer ARMS–PCR assay can be used for the rapid, species identity authentication of P. ginseng material in ginseng products. This assay can be used to complement chemical analytical methods in quality control, so both species identity and processing attributes of ginseng products can be efficiently addressed.

Background: Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis. Methods: Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to 1 July 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle–Ottawa Scale. The heterogeneity of the results was assessed with I2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted. Results: A total of 626 studies were retrieved, and 18 studies were fina lly included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE. Conclusions: This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation.

Abstract Human telomeres are linked to genetic instability and a higher risk of developing cancer. Therefore, to improve the dismal prognosis of pancreatic cancer patients, a thorough investigation of the association between telomere-related genes and pancreatic cancer is required. Combat from the R package “SVA” was performed to correct the batch effects between the TCGA-PAAD and GTEx datasets. After differentially expressed genes (DEGs) were assessed, we constructed a prognostic risk model through univariate Cox regression, LASSO-Cox regression, and multivariate Cox regression analysis. Data from the ICGC, GSE62452, GSE71729, and GSE78229 cohorts were used as test cohorts for validating the prognostic signature. The major impact of the signature on the tumor microenvironment and its response to immune checkpoint drugs was also evaluated. Finally, PAAD tissue microarrays were fabricated and immunohistochemistry was performed to explore the expression of this signature in clinical samples. After calculating 502 telomere-associated DEGs, we constructed a three-gene prognostic signature (DSG2, LDHA, and RACGAP1) that can be effectively applied to the prognostic classification of pancreatic cancer patients in multiple datasets, including TCGA, ICGC, GSE62452, GSE71729, and GSE78229 cohorts. In addition, we have screened a variety of tumor-sensitive drugs targeting this signature. Finally, we also found that protein levels of DSG2, LDHA, and RACGAP1 were upregulated in pancreatic cancer tissues compared to normal tissues by immunohistochemistry analysis. We established and validated a telomere gene-related prognostic signature for pancreatic cancer and confirmed the upregulation of DSG2, LDHA, and RACGAP1 expression in clinical samples, which may provide new ideas for individualized immunotherapy.

Abstract In patients receiving surgery, increased blood pressure variability may contribute to the onset of acute kidney injury (AKI). However, the extent and significance of blood pressure variability in patients undergoing aortic dissection surgery have yet to be determined. The authors analyzed all patients operated for aortic dissection at Peking University Shenzhen Hospital from January 1, 2011 to December 31, 2021. Preoperative blood pressure variability was expressed as standard deviation, coefficient of variation (CV), and range. The primary outcome was postoperative AKI. After multivariate analysis, systolic blood pressure variability was found to be independently associated with AKI after aortic dissection surgery. The odds ratios and 95% confidence intervals for standard deviation, CV, and systolic blood pressure range were 1.232 (1.011–1.500), 1.451 (1.058–1.991), and 1.138 (0.986–1.288) for postoperative AKI, respectively. However, there was no significant relationship between diastolic blood pressure variability and AKI after aortic dissection surgery. Finally, in patients undergoing surgery for aortic dissection, the variability of systolic blood pressure is actually an important factor in the development of AKI.

Salinity is a major factor limiting rice productivity, and developing salt-tolerant (ST) varieties is the most efficient approach. Seventy-eight ST introgression lines (ILs), including nine promising lines with improved ST and yield potential (YP), were developed from four BC2F4 populations from inter-subspecific crosses between an elite Geng (japonica) recipient and four Xian (indica) donors at the Institute of Crop Sciences, Chinese Academy of Agricultural Sciences. Genome-wide characterization of donor introgression identified 35 ST QTLs, 25 of which harbor 38 cloned ST genes as the most likely QTL candidates. Thirty-four are Xian-Geng differentiated ones with the donor (Xian) alleles associated with ST, suggesting differentiated responses to salt stress were one of the major phenotypic differences between the two subspecies. At least eight ST QTLs and many others affecting yield traits were identified under salt/non-stress conditions. Our results indicated that the Xian gene pool contains rich ‘hidden’ genetic variation for developing superior Geng varieties with improved ST and YP, which could be efficiently exploited by selective introgression. The developed ST ILs and their genetic information on the donor alleles for ST and yield traits would provide a useful platform for developing superior ST and high-yield Geng varieties through breeding by design in the future.

Abstract Background Tea, the second largest consumer beverage in the world after water, is widely cultivated in tropical and subtropical areas. However, the effect of environmental factors on the distribution of wild tea plants is unclear. Results A total of 159 wild tea plants were collected from different altitudes and geological types of the Guizhou Plateau. Using the genotyping-by-sequencing method, 98,241 high-quality single nucleotide polymorphisms were identified. Genetic diversity, population structure analysis, principal component analysis, phylogenetic analysis, and linkage disequilibrium were performed. The genetic diversity of the wild tea plant population from the Silicate Rock Classes of Camellia gymnogyna was higher than that from the Carbonate Rock Classes of Camellia tachangensis. In addition, the genetic diversity of wild tea plants from the second altitude gradient was significantly higher than that of wild tea plants from the third and first altitude gradients. Two inferred pure groups (GP01 and GP02) and one inferred admixture group (GP03) were identified by population structure analysis and were verified by principal component and phylogenetic analyses. The highest differentiation coefficients were determined for GP01 vs. GP02, while the lowest differentiation coefficients were determined for GP01 vs. GP03. Conclusions This study revealed the genetic diversity and geographical distribution characteristics of wild tea plants in the Guizhou Plateau. There are significant differences in genetic diversity and evolutionary direction between Camellia tachangensis with Carbonate Rock Classes at the first altitude gradient and Camellia gymnogyna with Silicate Rock Classes at the third altitude gradient. Geological environment, soil mineral element content, soil pH, and altitude markedly contributed to the genetic differentiation between Camellia tachangensis and Camellia gymnogyna.

Abstract Background Studying the genetic characteristics of tea plant (Camellia spp.) leaf traits is essential for improving yield and quality through breeding and selection. Guizhou Plateau, an important part of the original center of tea plants, has rich genetic resources. However, few studies have explored the associations between tea plant leaf traits and single nucleotide polymorphism (SNP) markers in Guizhou. Results In this study, we used the genotyping-by-sequencing (GBS) method to identify 100,829 SNP markers from 338 accessions of tea germplasm in Guizhou Plateau, a region with rich genetic resources. We assessed population structure based on high-quality SNPs, constructed phylogenetic relationships, and performed genome-wide association studies (GWASs). Four inferred pure groups (G-I, G-II, G-III, and G-IV) and one inferred admixture group (G-V), were identified by a population structure analysis, and verified by principal component analyses and phylogenetic analyses. Through GWAS, we identified six candidate genes associated with four leaf traits, including mature leaf size, texture, color and shape. Specifically, two candidate genes, located on chromosomes 1 and 9, were significantly associated with mature leaf size, while two genes, located on chromosomes 8 and 11, were significantly associated with mature leaf texture. Additionally, two candidate genes, located on chromosomes 1 and 2 were identified as being associated with mature leaf color and mature leaf shape, respectively. We verified the expression level of two candidate genes was verified using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and designed a derived cleaved amplified polymorphism (dCAPS) marker that co-segregated with mature leaf size, which could be used for marker-assisted selection (MAS) breeding in Camellia sinensis. Conclusions In the present study, by using GWAS approaches with the 338 tea accessions population in Guizhou, we revealed a list of SNPs markers and candidate genes that were significantly associated with four leaf traits. This work provides theoretical and practical basis for the genetic breeding of related traits in tea plant leaves.

Purpose: We report a rare, likely pathogenic variant gene causing Leber's hereditary optic neuropathy (LHON) in three-generation female members of an African-American family. Observations: The granddaughter and mother presented with a subacute, painless visual loss in both eyes at age 10 and 42 years to legal blindness. The maternal grandmother presented with a gradual onset of moderate visual loss at age 60. The mother and grandmother reported a history of bariatric surgery and subsequent vitamin deficiencies. All three patients shared similar Optical Coherent Tomography (OCT) findings of profound thinning of ganglion cell complex (GCC) and relatively preserved peripapillary retinal nerve fiber layer thickness (pRNFL). Nuclear and mitochondrial DNA sequencing identified a 14596A > T likely pathogenic variant, p.(Ile26Met), in the MT-ND6 gene, with 100% homoplasmy in the granddaughter and mother and 65% heteroplasmy in the grandmother. The mother and grandmother were treated with idebenone in addition to vitamin supplements, with a slight improvement in their vision. Conclusions and Importance: Our patients’ presentation stresses the importance of including LHON in the differential diagnosis in females presenting with unexplained bilateral, painless, severe visual loss. The OCT finding of profound GCC thinning with relatively preserved pRNFL thickness can be a red flag for LHON. A collaboration with genetic specialists to utilize expanded gene sequencing may greatly enhance our ability to identify rare pathogenic variants.

Abstract Based on the density functional theory (DFT), we investigate the friction properties of inevitable oxidized black phosphorus (o-BP). o-BP with the weaker interlayer adhesion exhibits their great potential as a solid lubricant. At the zero load, the friction property of o-BP is adjusted by its oxidation degree. Expressly, ultra-low friction of P4O2 (50% oxidation, O : P = 2 : 4 = 50%) is obtained, which is attributed to the upper O atoms with lower sliding resistance in the O channel formed by lower layer O atoms. More attractive, we observe superlubricity behavior of o-BP at the critical load/distance due to the flattening potential energy surface (PES). The flattening PES is controlled by the electrostatic role for the high-load (P4O3, O : P = 3 : 4 = 75%), and by the electrostatic and dispersion roles for the low-load (P4O2). Distinctly, the transform from ultra-low friction to superlubricity state of black phosphorus (BP) can be achieved by critical oxidation and load, which shows an important significance in engineering application. In addition, negative friction behavior of o-BP is a general phenomenon (Z > Zmin, Zmin is the interlayer distances between the outermost P atoms of minimum load.), while its surface-surface model is different from the fold mechanism of the tip-surface model (Z0 < Z < Zmin, Z0 is the interlayer distances between the outermost P atoms of equilibrium state.). Thus, this phenomenon cannot be captured due to the jump effect with instability of the atomic force microscopy (AFM) (Z > Zmin). In summary, o-BP improves the friction performance and reduces the application limitation, comparing to graphene (Gr), MoS2, and their oxides.

Abstract Background Genetic background plays an important role in the occurrence and development of gastric cancer (GC). With the application of genome-wide association study (GWAS), an increasing number of tumor susceptibility genes in gastric cancer have been discovered. While little of them can be further applicated in clinical diagnosis and treatment due to the lack of in-depth analysis. Methods A GWAS of peripheral blood leukocytes from GC patients was performed to identify and obtain genetic background data. In combination with a clinical investigation, key SNP mutations and mutated genes were screened. Via in vitro and in vivo experiments, the function of the mutated gene was verified in GC. Via a combination of molecular function studies and amino acid network analysis, co-mutations were discovered and further identified as potential therapeutic targets. Results At the genetic level, the G allele of rs104886038 in DHCR7 was a protective factor identified by the GWAS. Clinical investigation showed that patients with the rs104886038 A/G genotype, age ≥ 60, smoking ≥ 10 cigarettes/day, heavy drinking and H. pylori infection were independent risk factors for GC, with odds ratios of 12.33 (95% CI, 2.10 ~ 72.54), 20.42 (95% CI, 2.46 ~ 169.83), and 11.39 (95% CI, 1.82 ~ 71.21), respectively. Then molecular function studies indicated that DHCR7 regulated cell proliferation, migration, and invasion as well as apoptosis resistance via cellular cholesterol biosynthesis pathway. Further amino acid network analysis based on the predicted structure of DHCR7 and experimental verification indicated that rs104886035 and rs104886038 co-mutation reduced the stability of DHCR7 and induced its degradation. DHCR7 mutation suppressed the malignant behaviour of GC cells and induced apoptosis via inhibition on cell cholesterol biosynthesis. Conclusion In this work, we provided a comprehensive multi-dimensional analysis strategy which can be applied to in-depth exploration of GWAS data. DHCR7 and its mutation sites identified by this strategy are potential theratic targets of GC via inhibition of cholesterol biosynthesis.

Abstract Skin-integrated haptic interfaces that can relay a wealth of information from the machine to the human are of great interest. However, existing haptic devices are not yet able to produce haptic cues that are compatible with the skin. In this work, we present the stretchable soft actuators for haptic feedback, which can match the perception range, spatial resolution, and stretchability of the skin. Pressure-amplification structures are fabricated using a scalable self-assembly process to ensure an output pressure beyond the skin perception threshold. Due to the minimized device size, the actuator array can be fabricated with a sufficiently high spatial resolution, which makes the haptic device applicable for skin locations with the highest spatial acuity. A haptic feedback system is demonstrated by employing the developed soft actuators and highly sensitive pressure sensors. Two proof-of-concept applications are developed to illustrate the capability of transferring information related to surface textures and object shapes acquired at the robot side to the user side.

Graphene quantum dot (GQD) is a new type of carbon nanometer material. In addition to the excellent properties of graphene, it is superior due to the quantum limit effect and edge effect. Because of its advantages such as water solution, strong fluorescent, small size, and low biological toxicity, it has important application potential in various fields, especially in sensors and biomedical areas, which are mainly used as optical electrical sensors as well as in biological imaging and tumor therapy. In addition, GQDs have very important characteristics, such as optical and electrical properties. There are many preparation methods, divided into top-down and bottom-up methods, which have different advantages and disadvantages, respectively. In addition, the modification methods include heterogeneous doping, surface heterogeneity, etc. There are still many challenges in developing GQDs. For example, the synthesis steps are still hard to conduct, but as the inquiry continues to deepen, GQDs will be revolutionary materials in the future. In this work, the literature concerning research progress on GQDs has been reviewed and summarized, while the key challenges of their application have been pointed out, which may bring new insights to the application of GQDs.

Fiber optic gyroscope (FOG)-based north finding is extensively applied in navigation, positioning, and various fields. In dynamic north finding, an accelerated turntable speed shortens the time required for north finding, resulting in a rapid north-finding response. However, with an increase in turntable speed, the turntable’s jitter contributes to signal contamination in the FOG, leading to a deterioration in north-finding accuracy. This paper introduces a divide-and-conquer algorithm, the segmented cross-correlation algorithm, designed to mitigate the impact of turntable speed jitter. A model for north-finding error is established and analyzed, incorporating FOG’s self-noise and the turntable’s speed jitter. To validate the feasibility of our method, we implemented the algorithm on a FOG. The simulation and experimental results exhibited a strong concordance, affirming the validity of our proposed north-finding error model. The experimental findings indicate that, at a turntable speed of 180°/s, the north-finding bias error within a 360 s duration is 0.052°, representing a 64% improvement over the traditional algorithm. These results indicate the effectiveness of the proposed algorithm in mitigating the impact of unstable turntable speeds, offering a solution for north finding with both prompt response and enhanced accuracy.

The initial momentum along laser propagation plays a significant role in the electron dynamics during tunneling ionization. Our study shows that the offset emission angle decreases with increasing lateral momentum. By using three-dimensional strong-field approximation calculations with initial transverse momentum and a Coulomb correction, we accurately reproduce the transverse momentum-dependent angular shifts of Ar, Kr, and Xe atoms. We find that these shifts are attributed to the influence of initial momentum, tunneling exits, and a long-range Coulomb potential during electron propagation. Additionally, we establish a formula to reconstruct the initial transverse momentum from the final transverse momentum. The result may provide another perspective on attosecond angular streaking, which is crucial for understanding the influence of the Coulomb potential on electron motion.

BackgroundObservational studies have reported the association between fatigue and coronary artery disease (CAD), but the causal association between fatigue and CAD is unclear.MethodWe conducted a bidirectional Mendelian randomization (MR) study using publicly available genome-wide association studies (GWAS) data. The inverse-variance weighted (IVW) method was used as the primary analysis. We performed three complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) to evaluate the sensitivity and horizontal pleiotropy of the results.ResultSelf-reported fatigue had a causal effect on coronary artery atherosclerosis (CAA) (OR 1.047, 95%CI 1.033–1.062), myocardial infarction (MI) (OR 1.027 95%CI 1.014–1.039) and coronary heart disease (CHD) (OR 1.037, 95%CI 1.021–1.053). We did not find a significant reverse causality between self-reported fatigue and CAD. Given the heterogeneity revealed by MR-Egger regression, we employed the IVW random effect model. For the examination of fatigue on CHD and the reverse analysis of CAA, and MI on fatigue, the MR-PRESSO test found horizontal pleiotropy. No significant outliers were found.ConclusionThe MR analysis reveals a causal relationship between self-reported fatigue and CAD. The results should be interpreted with caution due to horizontal pleiotropy.

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes and pathways influencing the pathophysiology of SS and AS via bioinformatic analysis of microarray data.MethodsMicroarray datasets of SS (GSE40611) and AS (GSE28829) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired using R software’s “limma” packages, and the functions of common DEGs were determined using Gene Ontology and Kyoto Encyclopedia analyses. The protein–protein interaction (PPI) was established using the STRING database. The hub genes were assessed via cytoHubba plug-in and validated by external validation datasets (GSE84844 for SS; GSE43292 for AS). Gene set enrichment analysis (GSEA) and immune infiltration of hub genes were also conducted.ResultsEight 8 hub genes were identified using the intersection of four topological algorithms in the PPI network. Four genes (CTSS, IRF8, CYBB, and PTPRC) were then verified as important cross-talk genes between AS and SS with an area under the curve (AUC) ≥0.7. Furthermore, the immune infiltration analysis revealed that lymphocytes and macrophages are essentially linked with the pathogenesis of AS and SS. Moreover, the shared genes were enriched in multiple metabolisms and autoimmune disease-related pathways, as evidenced by GSEA analyses.ConclusionThis is the first study to explore the common mechanism between SS and AS. Four key genes, including CTSS, CYBB, IRF8, and PTPRC, were associated with the pathogenesis of SS and AS. These hub genes and their correlation with immune cells could be a potential diagnostic and therapeutic target.

BackgroundAlthough observational studies have shown that patients who experienced transient ischemic attacks (TIAs) had a higher risk of coronary artery disease (CAD), the causal relationship is ambiguous.MethodsWe conducted a two-sample Mendelian randomization (MR) study to analyze the causal relationship between TIA and CAD using data from the FinnGen genome-wide association study. Analysis was performed using the inverse-variance weighted (IVW) method. The robustness of the results was evaluated using MR-Egger regression, the weighted median, MR pleiotropy residual sum, and outlier (MR-PRESSO) and multivariable MR analysis.ResultsResults from IVW random-effect model showed that TIA was associated with an increased risk of coronary artery atherosclerosis (OR 1.17, 95% CI 1.06–1.28, P = 0.002), ischemic heart disease (OR 1.15, 95% CI 1.04–1.27, P = 0.007), and myocardial infarction (OR1.15, 95% CI 1.02–1.29, P = 0.025). In addition, heterogeneity and horizontal pleiotropy were observed in the ischemic heart disease results, while the sensitivity analysis revealed no evidence of horizontal pleiotropy in other outcomes.ConclusionsThis MR study demonstrated a potential causal relationship between TIA and CAD. Further research should be conducted to investigate the mechanism underlying the association.

The development of new sustainable green road materials with bio-resin is a hot topic in pavement engineering. To improve the efficiency of lignin as a sustainable pavement material, an asphalt binder modified by lignin-based resin was prepared, and its properties were evaluated. Firstly, lignin was extracted from biomass (corn straw) by thermochemical method to prepare lignin-based phenol formaldehyde (LPF) resin. After that, LPF resin-modified asphalt and phenol formaldehyde (PF) resin-modified asphalt were prepared. Then the effects of LPF resin and PF resin on asphalt properties were evaluated by chemical analysis and rheological performance tests. The results showed that lignin was involved in resin synthesis, LPF resin with PF resin had similar thermogravimetric curves, and the thermal stability of LPF resin was slightly lower than PF resin. Both LPF resin and PF resin can increase the proportion of large-size molecules and elastic components of asphalt binder and enhance its high-temperature deformation recovery ability. Moreover, the fatigue performance and aging resistance of the binder were also enhanced by the addition of LPF resin and PF resin. Although the addition of LPF resin and PF resin will increase the G-R parameters of virgin asphalt binder, it can reduce the effect of aging on the G-R parameters of asphalt binder. It seems that LPF resin and PF resin can improve the cracking resistance of asphalt binders.

The deliberate introduction of the beneficial gene in crop plants through transgenic technology can provide enormous agricultural and economic benefits. However, the impact of commercialization of these crops on the ecosystem particularly on belowground soil biodiversity is still uncertain. Here, we examined and compared the effects of a non-transgenic maize cultivar and an insect-resistant transgenic maize cultivar genetically engineered with cry1Ah gene from Bacillus thuringiensis, on the rhizosphere bacterial community using 16S rDNA amplicon sequencing and soil metabolome profile using UPLC/MS analysis at six different growth stages. We found no significant differences in bacterial community composition and diversity at all growth stages between the two cultivars. The analysis of bacterial beta-diversity showed an evident difference in community structure attributed to plant different growth stages but not to the plant type. In contrast, the soil metabolic profile of transgenic maize differed from that of the non-transgenic plant at some growth stages, and most of the altered metabolites were usually related to the metabolism but not to the plant-microbe interaction related pathways. These results suggest that genetic modification with the cry1Ah gene-altered maize soil metabolism but had no obvious effect on the rhizosphere bacterial community.

Purpose – Since many global path planning algorithms cannot achieve the planned path with both safety and economy, this study aims to propose a path planning method for unmanned vehicles with a controllable distance from obstacles. Design/methodology/approach – First, combining satellite image and the Voronoi field algorithm (VFA) generates rasterized environmental information and establishes navigation area boundary. Second, establishing a hazard function associated with navigation area boundary improves the evaluation function of the A* algorithm and uses the improved A* algorithm for global path planning. Finally, to reduce the number of redundant nodes in the planned path and smooth the path, node optimization and gradient descent method (GDM) are used. Then, a continuous smooth path that meets the actual navigation requirements of unmanned vehicle is obtained. Findings – The simulation experiment proved that the proposed global path planning method can realize the control of the distance between the planned path and the obstacle by setting different navigation area boundaries. The node reduction rate is between 33.52% and 73.15%, and the smoothness meets the navigation requirements. This method is reasonable and effective in the global path planning process of unmanned vehicle and can provide reference to unmanned vehicles’ autonomous obstacle avoidance decision-making. Originality/value – This study establishes navigation area boundary for the environment based on the VFA and uses the improved A* algorithm to generate a navigation path that takes into account both safety and economy. This study also proposes a method to solve the redundancy of grid environment path nodes and large-angle steering and to smooth the path to improve the applicability of the proposed global path planning method. The proposed global path planning method solves the requirements of path safety and smoothness.

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been reported to play critical regulatory roles in tumorigenesis, serving as tumor biomarkers and therapeutic targets. However, the contributions of circRNAs to CRC tumorigenesis are unclear. In our study, high expression of circLDLR was found in CRC tissues and cells and was closely associated with the malignant progression and poor prognosis of CRC patients. We demonstrated that circLDLR boosts growth and metastasis of CRC cells in vitro and in vivo, and modulates cholesterol levels in vitro. Mechanistically, we showed that circLDLR competitively binds to miR-30a-3p and prevents it from reducing the SOAT1 level, facilitating the malignant progression of CRC. In sum, our findings illustrate that circLDLR participates in CRC tumorigenesis and metastasis via the miR-30a-3p/SOAT1 axis, serving as a potential biomarker and therapeutic target in CRC.

IntroductionMajor depressive disorder (MDD) is associated with low-grade inflammation, and anti-inflammatory treatment can help improve depressive symptoms. A recent study found that fluvoxamine (FLV) can reduce Interleukin-6 (IL-6) production via sigma-1 receptor in inflammation models. However, the anti- IL-6 effect of FLV in treating patients with MDD and whether it can contribute to antidepressant effects remain unclear.MethodsA total of 65 patients with MDD and 34 healthy controls were recruited at baseline, and 50 patients completed the FLV treatment for 2 months. We assessed depression and anhedonia and collected plasma IL-6 levels at baseline, 1 month, and 2 months after baseline. This study evaluated the changes in clinical measures and IL-6 during treatment and analyzed their association. Further subgroup analyses were conducted in patients with MDD with high, medium, or low IL-6.ResultsDepression and anhedonia were significantly improved in patients with MDD, while the IL-6 did not significantly change after the FLV treatment. However, IL-6 significantly declined after the FLV treatment among patients with MDD with higher baseline IL-6. No significant associations were found between the changes in depressive symptoms and IL-6.ConclusionOur study provided preliminary evidence suggesting that the anti-IL-6 effect of FLV might not play a vital role in its antidepressant treatment, at least in patients with MDD with low inflammation. However, for patients with MDD with higher IL-6, FLV can help reduce IL-6 significantly in the antidepressant treatment, which may help guide the individual treatment of MDD with higher IL-6 levels.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04160377, identifier NCT04160377.

Background: Although recurrence rates after radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) remain high, there are a limited number of novel, high-quality mathematical predictive models that can be used to assess early recurrence after RFCA in patients with AF. Purpose: To identify the preoperative serum biomarkers and clinical characteristics associated with post-RFCA early recurrence of AF and develop a novel risk model based on least absolute shrinkage and selection operator (LASSO) regression to select important variables for predicting the risk of early recurrence of AF after RFCA. Methods: This study collected a dataset of 136 atrial fibrillation patients who underwent RFCA for the first time at Peking University Shenzhen Hospital from May 2016 to July 2022. The dataset included clinical characteristics, laboratory results, medication treatments, and other relevant parameters. LASSO regression was performed on 100 cycles of data. Variables present in at least one of the 100 cycles were selected to determine factors associated with the early recurrence of AF. Then, multivariable logistic regression analysis was applied to build a prediction model introducing the predictors selected from the LASSO regression analysis. A nomogram model for early post-RFCA recurrence in AF patients was developed based on visual analysis of the selected variables. Internal validation was conducted using the bootstrap method with 100 resamples. The model’s discriminatory ability was determined by calculating the area under the curve (AUC), and calibration analysis and decision curve analysis (DCA) were performed on the model. Results: In a 3-month follow-up of AF patients (n = 136) who underwent RFCA, there were 47 recurrences of and 89 non-recurrences of AF after RFCA. P, PLR, RDW, LDL, and CRI-II were associated with early recurrence of AF after RFCA in patients with AF (p < 0.05). We developed a predictive model using LASSO regression, incorporating four robust factors (PLR, RDW, LDL, CRI-II). The AUC of this prediction model was 0.7248 (95% CI 0.6342–0.8155), and the AUC of the internal validation using the bootstrap method was 0.8403 (95% CI 0.7684–0.9122). The model demonstrated a strong predictive capability, along with favorable calibration and clinical applicability. The Hosmer–Lemeshow test indicated that there was good consistency between the predicted and observed values. Additionally, DCA highlighted the model’s advantages in terms of its clinical application. Conclusions: We have developed and validated a risk prediction model for the early recurrence of AF after RFCA, demonstrating strong clinical applicability and diagnostic performance. This model plays a crucial role in guiding physicians in preoperative assessment and clinical decision-making. This novel approach also provides physicians with personalized management recommendations.

PurposeTo explore the changes of bacterial flora in anophthalmic patients wearing ocular prosthesis (OP) and the microbiome diversity in conditions of different OP materials.MethodsA cross-sectional clinical study was conducted, involving 19 OP patients and 23 healthy subjects. Samples were collected from the upper, lower palpebral, caruncle, and fornix conjunctiva. 16S rRNA sequencing was applied to identify the bacterial flora in the samples. The eye comfort of each OP patient was determined by a questionnaire. In addition, demographics information of each participant was also collected.ResultsThe diversity and richness of ocular flora in OP patients were significantly higher than that in healthy subjects. The results of flora species analysis also indicated that in OP patients, pathogenic microorganisms such as Escherichia Shigella and Fusobacterium increased significantly, while the resident flora of Lactobacillus and Lactococcus decreased significantly. Within the self-comparison of OP patients, compared with Polymethyl Methacrylate (PMMA), prosthetic material of glass will lead to the increased colonization of opportunistic pathogens such as Alcaligenes, Dermabacter and Spirochaetes, while gender and age have no significant impact on ocular flora.ConclusionsThe ocular flora of OP patients was significantly different from that of healthy people. Abundant colonization of pathogenic microorganisms may have an important potential relationship with eye discomfort and eye diseases of OP patients. PMMA, as an artificial eye material, demonstrated potential advantages in reducing the colonization of opportunistic pathogens.

Purpose: To use a novel in vivo method to simulate a moving hip model. Then, measure the dynamic bone-to-bone distance, and analyze the ischiofemoral space (IFS) of patients diagnosed with ischiofemoral impingement syndrome (IFI) during dynamic activities.Methods: Nine healthy subjects and 9 patients with IFI were recruited to collect MRI images and motion capture data. The motion trail of the hip during motion capture was matched to a personalized 3D hip model reconstructed from MRI images to get a dynamic bone model. This personalized dynamic in vivo method was then used to simulate the bone motion in dynamic activities. Validation was conducted on a 3D-printed sphere by comparing the calculated data using this novel method with the actual measured moving data using motion capture. Moreover, the novel method was used to analyze the in vivo dynamic IFS between healthy subjects and IFI patients during normal and long stride walking.Results: The validation results show that the root mean square error (RMSE) of slide and rotation was 1.42 mm/1.84° and 1.58 mm/2.19°, respectively. During normal walking, the in vivo dynamic IFS was significantly larger in healthy hips (ranged between 15.09 and 50.24 mm) compared with affected hips (between 10.16 and 39.74 mm) in 40.27%–83.81% of the gait cycle (p = 0.027). During long stride walking, the in vivo dynamic IFS was also significantly larger in healthy hips (ranged between 13.02 and 51.99 mm) than affected hips (between 9.63 and 44.22 mm) in 0%–5.85% of the gait cycle (p = 0.049). Additionally, the IFS of normal walking was significantly smaller than long stride walking during 0%–14.05% and 85.07%–100% of the gait cycle (p = 0.033, 0.033) in healthy hips. However, there was no difference between the two methods of walking among the patients.Conclusions: This study established a novel in vivo method to measure the dynamic bone-to-bone distance and was well validated. This method was used to measure the IFS of patients diagnosed with IFI, and the results showed that the IFS of patients is smaller compared with healthy subjects, whether in normal or long stride walking. Meanwhile, IFI eliminated the difference between normal and long stride walking.

The soluble solid content (SSC) is one of the important parameters depicting the quality, maturity and taste of fruits. This study explored hyperspectral imaging (HSI) and fluorescence spectral imaging (FSI) techniques, as well as suitable chemometric techniques to predict the SSC in kiwifruit. 90 kiwifruit samples were divided into 70 calibration sets and 20 prediction sets. The hyperspectral images of samples in the spectral range of 387 nm~1034 nm and the fluorescence spectral images in the spectral range of 400 nm~1000 nm were collected, and their regions of interest were extracted. Six spectral pre-processing techniques were used to pre-process the two spectral data, and the best pre-processing method was selected after comparing it with the predicted results. Then, five primary and three secondary feature extraction algorithms were used to extract feature variables from the pre-processed spectral data. Subsequently, three regression prediction models, i.e., the extreme learning machines (ELM), the partial least squares regression (PLSR) and the particle swarm optimization - least square support vector machine (PSO-LSSVM), were established. The prediction results were analyzed and compared further. MASS-Boss-ELM, based on fluorescence spectral imaging technique, exhibited the best prediction performance for the kiwifruit SSC, with the Rp2, Rc2 and RPD of 0.8894, 0.9429 and 2.88, respectively. MASS-Boss-PLSR based on the hyperspectral imaging technique showed a slightly lower prediction performance, with the Rp2, Rc2, and RPD of 0.8717, 0.8747, and 2.89, respectively. The outcome presents that the two spectral imaging techniques are suitable for the non-destructive prediction of fruit quality. Among them, the FSI technology illustrates better prediction, providing technical support for the non-destructive detection of intrinsic fruit quality.

The purpose of this study is to establish a life prediction model of lithium-thiocarbonyl chloride batteries by semi-empirical method. In the experiment, accelerated life tests on several groups of batteries at different temperatures were conducted. After a period of operation in the range from 25 °C to 74 °C, it was found that the higher the temperature, the less the remaining capacity of the batteries. According to the study of the battery aging mechanism, the characteristic parameter impedance of an aging battery would change exponentially with the increase of storage time and environmental temperature. The established life prediction model showed that the change in battery impedance spectrum had a good law, which made it possible to predict the state of charge (SOC) of the battery according to the local change characteristics of the electrochemical impedance spectroscopy (EIS) spectrum. The experimental data were compared with the fitted prediction curve, and the maximum deviation of the prediction was only 4.1036%, which indicated that the constructed model had high accuracy.

The direct oxidation of methane to methanol as a liquid fuel and chemical feedstock is arguably the most desirable methane conversion pathway. Currently, constructing and understanding linear scaling relationships between the fundamental physical or chemical properties of catalysts and their catalytic performance to explore suitable descriptors is crucial for theoretical research on the direct conversion of methane to methanol. In this review, we summarize the energy, electronic, and structural descriptors used to predict catalytic activity. Fundamentally, these descriptors describe the redox properties of active sites from different dimensions. We further explain the moderate principle of descriptors in methane-to-methanol catalyst design and provide related application work. Simultaneously, the underlying activity limitation of methane activation and active species generation is revealed. Based on the selectivity descriptor, the inverse scaling relationship limitation between methane conversion and methanol selectivity is quantitatively understood. Finally, multiscale strategies are proposed to break the limitation and achieve the simultaneous enhancement of activity and selectivity. This descriptor-based review provides theoretical insights and guidance to accelerate the understanding, optimization, and design of efficient catalysts for direct methane-to-methanol conversion.

Obtaining ship navigation information from maritime videos can significantly improve maritime supervision efficiency and enable timely safety warnings. Ship detection and tracking are essential technologies for mining video information. However, current research focused on these advanced vision tasks in maritime supervision is not sufficiently comprehensive. Taking into account the application of ship detection and tracking technology, this study proposes a deep learning-based ship speed extraction framework under the haze environment. First, a lightweight convolutional neural network (CNN) is used to remove haze from images. Second, the YOLOv5 algorithm is used to detect ships in dehazed marine images, and a simple online and real-time tracking method with a Deep association metric (Deep SORT) is used to track ships. Then, the ship’s displacement in the images is calculated based on the ship’s trajectory. Finally, the speed of the ships is estimated by calculating the mapping relationship between the image space and real space. Experiments demonstrate that the method proposed in this study effectively reduces haze interference in maritime videos, thereby enhancing the image quality while extracting the ship’s speed. The mean squared error (MSE) for multiple scenes is 0.3 Kn on average. The stable extraction of ship speed from the video achieved in this study holds significant value in further ensuring the safety of ship navigation.

IntroductionSpinal cord injury (SCI) results in drastic dysregulation of microenvironmental metabolism during the acute phase, which greatly affects neural recovery. A better insight into the potential molecular pathways of metabolic dysregulation by multi-omics analysis could help to reveal targets that promote nerve repair and regeneration in the future.Materials and methodsWe established the SCI model and rats were randomly divided into two groups: the acute-phase SCI (ASCI) group (n = 14, 3 days post-SCI) and the sham group with day-matched periods (n = 14, without SCI). In each group, rats were sacrificed at 3 days post-surgery for histology study (n = 3), metabolome sequencing (n = 5), transcriptome sequencing (n = 3), and quantitative real-time polymerase chain reaction (n = 3). The motor function of rats was evaluated by double-blind Basso, Beattie, and Bresnahan (BBB) Locomotor Scores at 0, 1, 2, 3 days post-SCI in an open field area. Then the transcriptomic and metabolomic data were integrated in SCI model of rat to reveal the underlying molecular pathways of microenvironmental metabolic dysregulation.ResultsThe histology of the microenvironment was significantly altered in ASCI and the locomotor function was significantly reduced in rats. Metabolomics analysis showed that 360 metabolites were highly altered during the acute phase of SCI, of which 310 were up-regulated and 50 were down-regulated, and bioinformatics analysis revealed that these differential metabolites were mainly enriched in arginine and proline metabolism, D-glutamine and D-glutamate metabolism, purine metabolism, biosynthesis of unsaturated fatty acids. Transcriptomics results showed that 5,963 genes were clearly altered, of which 2,848 genes were up-regulated and 3,115 genes were down-regulated, and these differentially expressed genes were mainly involved in response to stimulus, metabolic process, immune system process. Surprisingly, the Integrative analysis revealed significant dysregulation of purine metabolism at both transcriptome and metabolome levels in the acute phase of SCI, with 48 differential genes and 16 differential metabolites involved. Further analysis indicated that dysregulation of purine metabolism could seriously affect the energy metabolism of the injured microenvironment and increase oxidative stress as well as other responses detrimental to nerve repair and regeneration.DiscussionOn the whole, we have for the first time combined transcriptomics and metabolomics to systematically analyze the potential molecular pathways of metabolic dysregulation in the acute phase of SCI, which will contribute to broaden our understanding of the sophisticated molecular mechanisms of SCI, in parallel with serving as a foundation for future studies of neural repair and regeneration after SCI.

Herein, a combined multipoint picking scheme was proposed, and the sizes of the end of the bud picker were selectively designed. Firstly, the end of the bud picker was abstracted as a fixed-size picking box, and it was assumed that the tea buds in the picking box have a certain probability of being picked. Then, the picking box coverage and the greedy algorithm were designed to make as few numbers of picking box set as possible to cover all buds to reduce the numbers of picking. Furthermore, the Graham algorithm and the minimum bounding box were applied to fine-tune the footholds of each picking box in the optimal coverage picking box set, so that the buds were concentrated in the middle of the picking boxes as much as possible. Moreover, the geometric center of each picking box was taken as a picking point, and the ant colony algorithm was used to optimize the picking path of the end of the bud picker. Finally, by analyzing the influence of several parameters on the picking performance of the end of the bud picker, the optimal sizes of the picking box were calculated successfully under different conditions. The experimental results showed that the average picking numbers of the combined multipoint picking scheme were reduced by 31.44%, the shortest picking path was decreased by 11.10%, and the average consumed time was reduced by 50.92% compared to the single-point picking scheme. We believe that the proposed scheme can provide key technical support for the subsequent design of intelligent bud-picking robots.

BackgroundThere is a relative lack of data that systematically investigates the breadth and validity of the association between bariatric surgery and health-related outcomes. We aimed to evaluate the quantity, validity, and credibility of evidence regarding the association between bariatric surgery and health-related outcomes using an umbrella review of meta-analyses.MethodsWe systematically searched PubMed, Embase, and the Web of Science databases from inception until December 2, 2021, to identify meta-analyses of observational or interventional studies that investigated the association between bariatric surgery and multiple health outcomes. We extracted the summary effect size and 95% confidence interval (CI) data. The Assessment of Multiple Systematic Reviews (AMSTAR-2) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines were used for methodological and evidence quality assessments, respectively.ResultsTwenty-eight studies with 82 different health-related outcomes were included in this umbrella review. Beneficial effects of bariatric surgery have been observed in cancer incidence, mortality, cardiovascular risk, polycystic ovary syndrome (PCOS), anxiety symptoms, depressive symptoms, gestational diabetes mellitus, gestational hypertension, large for gestational age (LGA), macrosomia, post-term birth, risk of kidney stones, albuminuria, urinary incontinence, fecal incontinence, Barrett’s esophagus, and diabetic retinopathy. However, adverse effects of bariatric surgery were observed for maternal anemia, perinatal mortality, congenital anomalies, preterm birth, neonatal intensive care unit (NICU) admission, intrauterine growth restriction, small for gestational age (SGA), fracture risk, upper limb fracture, suicide, self-harm, and alcohol use disorder (AUD).ConclusionsCurrent evidence suggests that bariatric surgery improves the majority of health-related outcomes; however, caution is advised given it may increase the risk of adverse mental effects, perinatal problems, and fractures.

Abstract Negative immune checkpoint blockade immunotherapy has shown potential for multiple malignancies including colorectal cancer (CRC). B7-H5, a novel negative immune checkpoint regulator, is highly expressed in tumor tissues and promotes tumor immune escape. However, the clinical significance of B7-H5 expression in CRC and the role of B7-H5 in the tumor microenvironment (TME) has not been fully clarified. In this study, we observed that high B7-H5 expression in CRC tissues was significantly correlated with the lymph node involvement, AJCC stage, and survival of CRC patients. A significant inverse correlation was also observed between B7-H5 expression and CD8+ T-cell infiltration in CRC tissues. Kaplan−Meier analysis showed that patients with high B7-H5 expression and low CD8+ T-cell infiltration had the worst prognosis in our cohort of CRC patients. Remarkably, both high B7-H5 expression and low CD8+ T infiltration were risk factors for overall survival. Additionally, B7-H5 blockade using a B7-H5 monoclonal antibody (B7-H5 mAb) effectively suppressed the growth of MC38 colon cancer tumors by enhancing the infiltration and Granzyme B production of CD8+ T cells. Importantly, the depletion of CD8+ T cells obviously abolished the antitumor effect of B7-H5 blockade in the MC38 tumors. In sum, our findings suggest that B7-H5 may be a valuably prognostic marker for CRC and a potential target for CRC immunotherapy.